Blood samples from 29 healthy individuals (control), 16 chronic alcohol abusers without clinical symptoms of liver disease, 22 patients with alcoholic steatosis and 31 patients with alcoholic cirrhosis were obtained. The antiviral activity, only partially neutralized by polyclonal and monoclonal anti-HuIFN-alpha and monoclonal anti-HuIFN-gamma antibodies, was detected in sera of 38% healthy controls and of 64-77% alcoholic abusers without or with ALD. To measure the activity of the IFN system, leukocyte cultures of chronic alcohol abusers and control individuals were set up using a whole blood technique. Common IFN inducers: NDV, PHA and ConA were used. Blood leukocytes of patients with alcoholic steatosis and cirrhosis responded to NDV, PHA and ConA with significantly lower IFN levels than controls, whereas IFN response of alcoholics without liver diseases was lower only after stimulation with ConA. Regarding the lymphoproliferative test performed with PHA, a remarkably diminished lymphocyte response of patients with cirrhosis was observed as compared to control. Our data indicate that long term ethanol intake impairs the ability of leukocytes and their subpopulation to produce IFNs. The correlation between ALD progression and the defect in IFN production suggests that suppressive action of ethanol, liver injury and immune reactions involved in liver damage may be responsible for impairment of the IFN system in heavy drinkers.